They can assess how many sperm a man produces, whether sperm are misshapen, and how well they swim. But that’s about it.

Determined to extract more data, several startups are developing next-generation tests that they hope will help men better understand their fertility. The goal: to explain why some men who have normal sperm counts still cannot conceive.

One such test, marketed as Seed, will be unveiled Monday in front of thousands of fertility doctors at the annual meeting of the American Society for Reproductive Medicine in Salt Lake City. The $895 test comes from a startup called Episona, which operates out of a historic Craftsman bungalow here in Pasadena. It works by analyzing 480,000 regions of the epigenome—a teeming collection of chemical compounds, different for each individual, that latch on to our DNA and affect which genes are turned on and off.

Founder Alan Horsager, who worked with geneticists, sperm experts, and computer scientists to develop the test, said he hoped to fill “a very big vacuum” for men struggling with infertility. “There’s a big hunger for information on the male side,” he said.

“I hate not knowing what’s wrong with my patients. It’s frustrating for me and heartbreaking for them,” said Dr. Richard Scott, a fertility specialist in New Jersey who helped Episona conduct a validation test of its technology and serves on its scientific advisory board.

“Reproduction is something we’re all supposed to be able to do,” Scott said. “When it’s not working, people need an explanation.”

The trouble is, that explanation doesn’t always point to a solution.

The Seed test, like others now in development, will help a man understand why he’s infertile even if his sperm looks normal under a microscope. But while doctors may advise those men to lose weight or stop smoking in an effort to improve their epigenetic profile, there’s no treatment yet.

That means, often, the test results will be most useful in driving home that the infertility is real. That knowledge could spur couples to consider sperm donors or adoption, instead of investing tens of thousands of dollars — and years of heartache—in cycle after cycle of in vitro fertilization.

“One of the most heartbreaking things we see is people go through one cycle of IVF, have poor quality embryos, and then go through a second cycle hoping it will be better,” said Doug Carrell, an endocrinologist at the University of Utah who studies sperm epigenetics and cofounded Episona. “My hope for the test is that we give them more knowledge beforehand.”

Nearly 5 million men in the US struggle with infertility, according to the Centers for Disease Control and Prevention. Male factors are primarily responsible in about 30 percent of couples who cannot conceive and play some role in about half of all infertility problems. As many of 30 percent of males have unexplained or “idiopathic” infertility.

Traditional sperm tests have drawn intensive criticism in recent years, in part because they’re subjective—based on technicians looking through microscopes—and can change from day to day.

Carrell is among fertility specialists who have been writing editorials and journal articles in recent years with titles like, “The troubling state of the semen analysis.”

“How many sperm do you have and how well do they swim? That’s been the gold standard forever,” said Scott. “Unfortunately, that’s a very unsophisticated view of a very complex problem.” For example, many men with a low sperm count, or sperm that are misshapen, are able to conceive. And many men with seemingly normal tests results aren’t. “We need much more powerful insights into this process,” Scott said.

Entrepreneurs are rushing to fill that gap.

Aytu BioSciences, based in Englewood, Colo., sells a lab test in Europe and the Middle East called MiOXSYS that detects oxidative stress in sperm; that’s a known factor in some male infertility. The company is seeking FDA approval for US sales.

Androvia Life Sciences, based in New York, is developing a test to see if sperm are able to undergo capacitation, physiological changes necessary for fertilization. (Tests to evaluate if DNA in sperm is damaged or “fragmented” have been available for decades, but the jury is still out on if this information is clinically useful.)

One new test that’s already on the market: Trak, from Bay Area startup Sandstone Diagnostics. The $200 device uses a small, desktop centrifuge to determine a man’s sperm count. The device lets men conduct the analysis at home, without involving a fertility clinic, but doesn’t offer more data than a traditional test.

The Seed test, which is sold through physicians’ offices, comes in a sleek black box decorated with bright blue chromosomes that looks more like packaging for an iPhone than a medical diagnostic. It includes a funnel and collection vial and return mailing label for the sample to be sent to a lab after it is collected at home. (It does not need to be refrigerated.) When results are ready, men can view them online at home shortly after they have been sent to the physician for review.

Fertility experts said the at-home collection process is a huge plus for men who are reluctant to generate sperm samples at a lab or quickly deliver them from home. “They’re like, ‘Are you kidding me? I have to go where and do what?’” said Barbara Collura, president and chief executive of RESOLVE, the National Infertility Association.

And while the test results don’t point to solutions, “it’s absolutely valuable” to get more insight into the causes of infertility, said Dr. Matthew Wosnitzer, a fertility expert in the Yale-New Haven Health System who is aware of the new test but was not involved in its development. “We don’t have that many tests for men, and the more data points you have the better.”

James Golembowski knows just how important that data can be. The New Jersey resident and his wife have been trying to conceive a baby for 11 years, nearly since their wedding day. Traditional sperm testing told him that he wasn’t producing sperm, but he still does not know why. A procedure to use sperm extracted from his testes also failed.

“In my case, I had limited answers, which weren’t helpful in dealing with the grief,” Golembowski said. He urges other men to take action as soon as they run into trouble conceiving. “I would advise starting testing the minute a problem is suspected,” he said.

ABOUT THE AUTHOR(S)

Usha Lee McFarling

Usha Lee McFarling, the West Coast correspondent for STAT, covers the people and trends behind biomedical advances in the western U.S. She previously reported for the Los Angeles Times, Boston Globe, Knight Ridder Washington Bureau, and the San Antonio Light, where she covered killer bees, bat rabies outbreaks, and cases of leprosy linked to armadillo taxidermy. Her work on the diseased state of the world's oceans earned the 2007 Pulitzer Prize for explanatory journalism. Usha graduated from Brown University with a degree in biology and later earned a masters degree at Berkeley after spending years studying the behavior of desert woodrats. When not writing, she can be found on the closest ski slope -- especially during El Nino years.

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